Prostate cancer is a commonly diagnosed cancer in men and a leading cause of cancer death. If detected at an early and treatable stage, prostate cancer is curable. Unfortunately, a majority of cases are diagnosed at later stages when metastasis of the primary tumor has already occurred. Even early diagnosis is controversial because not all individuals who test positive in prostate cancer screens develop cancer.
Prostate specific antigen (PSA) is a serum glycoprotein member of the glandular kallikrein gene family. PSA has a restricted chymotrypsin-like enzyme activity cleaving C-terminally to tyrosine and leucine residues on semenogelin I, the natural substrate of PSA. The tissue specificity of PSA makes it useful as both a diagnostic target and as a potential therapeutic target for active specific immunotherapy. Prostate specific antigen can be detected at low levels in the sera of healthy males without clinical evidence of prostate cancer. During neoplastic states, however, circulating levels of PSA increase dramatically. These increases frequently correlate with the clinical stage of the disease. Therefore, PSA is widely used as a marker for both screening and stratification of prostate cancer, with levels greater than 4 ng/mL considered to be a reliable indicator of prostate cancer (Jeong 2007). In serum, two different forms of PSA are immunologically detectable: a free form (MW=30 kDa) and a complex with α-1-antichymotrypsin (ACT-PSA, MW=100 kDa). Equimolar total PSA determination (free PSA+ACT-PSA), the ratio between total PSA and free PSA, digital rectal examination (DRE), and biopsy are included in multiple prostate cancer diagnostic algorithms. The ratio between total PSA and free PSA also may provide distinguishing information between cancer and benign prostatic hyperplasia (BPH), which is a common misdiagnosis. Measuring total PSA for diagnostic or follow-up purposes requires assays that detect a broad range (0.1 to 20 ng/mL) of concentrations (Acevedo 2002).
Current PSA screening tests utilize a monoclonal antibody (mAb) as a capture agent to detect PSA in a blood sample. These tests have several limitations inherent to monoclonal antibody technology. First, monoclonal antibody instability results significant costs and limitations in shipping, handling, and storage. Second, monoclonal antibodies are not exact chemical structures, meaning they can exhibit significant batch-to-batch variation in composition. This can lead to variations in capture affinity and selectivity between batches, leading to issues with the quantitative character of protein assays. Consequently, there is a need in the art for improved PSA capture agents to replace monoclonal antibodies for use in both screening for and treating prostate cancer.